Fulvestrant-3-Boronic Acid (ZB716) Demonstrates Oral Bioavailability and Favorable Pharmacokinetic Profile in Preclinical ADME Studies
Fulvestrant-3-boronic acid (ZB716), an oral selective estrogen receptor degrader (SERD) under clinical development, has been investigated in ADME studies to characterize its absorption, metabolism, and pharmacokinetics. ZB716 was found to have high plasma protein binding in human and animal plasma, and low intestinal mucosal permeability. ZB716 had high clearance in hepatocytes of all species tested. ZB716 was metabolized primarily by CYP2D6 and CYP3A. In human liver microsomes, ZB716 demonstrated relatively low inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (when testosterone was used as the substrate), and no inhibition of CYP2B6 and 3A4 (when midazolam was used as the substrate). In assays for enzyme activity, ZB716 induced CYP1A2, 2B6, and 3A4 in a concentration-dependent manner. Single-dose and repeated-dose pharmacokinetic studies in rats and dogs showed oral bioavailability, dose-proportional drug exposure, and drug accumulation as measured by maximum concentration and area under the concentration-time curve (AUC).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Pharmaceuticals (Basel, Switzerland) - 14(2021), 8 vom: 26. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Jiawang [VerfasserIn] |
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| Links: |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
Date Revised 04.11.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/ph14080719 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329946404 |
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| 520 | |a Fulvestrant-3-boronic acid (ZB716), an oral selective estrogen receptor degrader (SERD) under clinical development, has been investigated in ADME studies to characterize its absorption, metabolism, and pharmacokinetics. ZB716 was found to have high plasma protein binding in human and animal plasma, and low intestinal mucosal permeability. ZB716 had high clearance in hepatocytes of all species tested. ZB716 was metabolized primarily by CYP2D6 and CYP3A. In human liver microsomes, ZB716 demonstrated relatively low inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (when testosterone was used as the substrate), and no inhibition of CYP2B6 and 3A4 (when midazolam was used as the substrate). In assays for enzyme activity, ZB716 induced CYP1A2, 2B6, and 3A4 in a concentration-dependent manner. Single-dose and repeated-dose pharmacokinetic studies in rats and dogs showed oral bioavailability, dose-proportional drug exposure, and drug accumulation as measured by maximum concentration and area under the concentration-time curve (AUC) | ||
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| 650 | 4 | |a oral bioavailability | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a selective estrogen receptor degrader | |
| 700 | 1 | |a Rajasekaran, Nirmal |e verfasserin |4 aut | |
| 700 | 1 | |a Hossain, Ahamed |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Changde |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Shanchun |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Borui |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Hunsoon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hongjoong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guangdi |e verfasserin |4 aut | |
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